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Metabolic fates of pyruvate
Metabolic fates of pyruvate
4/25/2019 Biochemistry for medics 3
Pyruvate dehydrogenase complex (PDH complex) = made up of 3 enzymes
converts pyruvate to acetylCoA
Pyruvate dehydrogenase
Dihydrolipoyl transacetylase
Dihydrolipoyl dehydrogenase
Five different coenzymes or prosthetic groups:ty:
1. Thiamine pyrophosphate (TPP)
2. Flavin adenine dinucleotide (FAD)
3. Coenzyme A (CoA, sometimes denoted CoA-SH, to emphasize the role of the -
SH group),
4. Nicotinamide adenine dinucleotide (NAD),
5. Lipoate.
Four different vitamins are vital components of this system: thiamine (in TPP),
riboflavin (in FAD), niacin (in NAD), and pantothenate (in CoA).
Pyruvate Dehydrogenase complex
PDH complex = made up of 3 enzymes and require five coenzymes for
activity (NAD, FAD, Lipoic acids, coenzyme A and TPP)
Kreb’s cycle
4/25/2019 Biochemistry for medics 5
Overview of the Citric Acid Cycle
The citric acid cycle (Kreb’s cycle or tricarboxylic acid cycle) includes a
series of oxidation-reduction reactions
There is oxidation of an acetyl group to two molecules of carbon
dioxide
and reduce the coenzymes that are re-oxidized through the electron
transport chain, linked to the formation of ATP.
4/25/2019 6
Biochemistry for medics
TCA cycle
The citric acid cycle is the central metabolic hub of the cell.
 It is the final common pathway for the oxidation of fuel molecule
such as amino acids, fatty acids, and carbohydrates.
In eukaryotes, the reactions of the citric acid cycle take place inside
mitochondria, in contrast with those of glycolysis, which take place in
the cytosol.
4/25/2019 Biochemistry for medics 8
TCA cycle
Oxidative decarboxylation
Oxidative decarboxylation
dehydrogenation
dehydrogenation
Substrate level
phosphorylation
Oxaloacetate
Isocitrate dehydrogenase
Malate dehydrogenase
Cont…
• In each turn of TCA, one acetyl group enters as acetyl-CoA and 2
molecules of CO2 are produced
• One molecule of OAA can theoretically bring about oxidation of an
infinite number of acetyl group
• In fact, OAA conc. in cells is very low
4/25/2019 Biochemistry for medics 9
Amphibolic pathway
• TCA = amphibolic pathway = one that serves in both
catabolic and anabolic processes
• TCA role is not limited to energy conservation.
• 4 or 5 carbons end product of many catabolic
processes feed into the cycle to serve as fuel
• E.g. OAA and α-KG produced from Asp and Glu
4/25/2019 Biochemistry for medics 10
• Under some circumstances intermediates are drawn
out of cycle to be used as precursors in a variety of
biosynthetic pathways.
• E.g. α-KG and OAA = can serve as precursors of amino
acid Glu and Asp by simple transamination reaction
4/25/2019 Biochemistry for medics 11
Anaplerotic reactions
• When intermediates are taken from the TCA cycle to
other pathways, they are replenished by several
anaplerotic reactions,
• To replace removed intermediates, cells employ
replenishing reactions (anaplerotic reactions)
4/25/2019 Biochemistry for medics 12

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A141656821_23691_25_2019_Kreb cycle.pdf

  • 3. 4/25/2019 Biochemistry for medics 3 Pyruvate dehydrogenase complex (PDH complex) = made up of 3 enzymes converts pyruvate to acetylCoA Pyruvate dehydrogenase Dihydrolipoyl transacetylase Dihydrolipoyl dehydrogenase Five different coenzymes or prosthetic groups:ty: 1. Thiamine pyrophosphate (TPP) 2. Flavin adenine dinucleotide (FAD) 3. Coenzyme A (CoA, sometimes denoted CoA-SH, to emphasize the role of the - SH group), 4. Nicotinamide adenine dinucleotide (NAD), 5. Lipoate. Four different vitamins are vital components of this system: thiamine (in TPP), riboflavin (in FAD), niacin (in NAD), and pantothenate (in CoA).
  • 4. Pyruvate Dehydrogenase complex PDH complex = made up of 3 enzymes and require five coenzymes for activity (NAD, FAD, Lipoic acids, coenzyme A and TPP)
  • 6. Overview of the Citric Acid Cycle The citric acid cycle (Kreb’s cycle or tricarboxylic acid cycle) includes a series of oxidation-reduction reactions There is oxidation of an acetyl group to two molecules of carbon dioxide and reduce the coenzymes that are re-oxidized through the electron transport chain, linked to the formation of ATP. 4/25/2019 6 Biochemistry for medics
  • 7. TCA cycle The citric acid cycle is the central metabolic hub of the cell.  It is the final common pathway for the oxidation of fuel molecule such as amino acids, fatty acids, and carbohydrates. In eukaryotes, the reactions of the citric acid cycle take place inside mitochondria, in contrast with those of glycolysis, which take place in the cytosol.
  • 8. 4/25/2019 Biochemistry for medics 8 TCA cycle Oxidative decarboxylation Oxidative decarboxylation dehydrogenation dehydrogenation Substrate level phosphorylation Oxaloacetate Isocitrate dehydrogenase Malate dehydrogenase
  • 9. Cont… • In each turn of TCA, one acetyl group enters as acetyl-CoA and 2 molecules of CO2 are produced • One molecule of OAA can theoretically bring about oxidation of an infinite number of acetyl group • In fact, OAA conc. in cells is very low 4/25/2019 Biochemistry for medics 9
  • 10. Amphibolic pathway • TCA = amphibolic pathway = one that serves in both catabolic and anabolic processes • TCA role is not limited to energy conservation. • 4 or 5 carbons end product of many catabolic processes feed into the cycle to serve as fuel • E.g. OAA and α-KG produced from Asp and Glu 4/25/2019 Biochemistry for medics 10
  • 11. • Under some circumstances intermediates are drawn out of cycle to be used as precursors in a variety of biosynthetic pathways. • E.g. α-KG and OAA = can serve as precursors of amino acid Glu and Asp by simple transamination reaction 4/25/2019 Biochemistry for medics 11
  • 12. Anaplerotic reactions • When intermediates are taken from the TCA cycle to other pathways, they are replenished by several anaplerotic reactions, • To replace removed intermediates, cells employ replenishing reactions (anaplerotic reactions) 4/25/2019 Biochemistry for medics 12